neruoimaging final

NEUROIMAGING IN PSYCHIATRY

Presenter-Dr.Swapnil Agrawal

Resident,Dept. of Psychiatry,

Govt. Medical College, Kota

Contents- Basic fundamentals about-

CT scan MRI MRS fMRI SPECT PET

Imaging in some specific psychiatric disorders- Imaging in Dementia Imaging in OCD Imaging in Depression & Bipolar disorders Imaging in Schizophrenia Imaging in Anxiety disorders & PTSD Imaging in ADHD & Autism

NEUROIMAGING

Can allow measurement of the structure, function, & chemistry of the living human brain

Has provided new information about the pathophysiology of psychiatric disorders

Can be useful for diagnosing illness, predicting prognosis & for developing new treatments

Indications in Clinical Practice

Neurological Deficits

To rule out neurological causes of psychiatric illnesses

Dementia

USES OF NEUROIMAGING

Indications in Clinical Research

Analysis of Clinically Defined Groups of Patients

Analysis of Brain Activity during Performance of Specific Tasks

1. Structural Plain Skull Radiography Pneumo-encephalography CT scan Structural MRI

2. Functional Magnetic resonance spectroscopy (MRS) Functional MRI (fMRI) Positron emission tomography (PET) Single photon emission computed tomography (SPECT) Brain electrical activity mapping (BEAM) Evoked Potential

NEURO-IMAGING TECHNIQUES

COMPUTED TOMOGRAPHY (CT)

…Contd

CT Scanners take a series of head X-ray

pictures from all vantage points

360º around a patient's head

The amount of radiation that passes through, or is not absorbed from, each

angle is digitized & entered into a computer

The computer uses matrix algebra calculations to assign a specific

density to each point within the head & displays these data as a set of 2-D

images

When viewed in sequence, the images

allow mental reconstruction of the structure of the brain

BASICS

Grey-scale Appearance on CT

Tissue Appearance

Bone White

Calcified Tissue White

Clotted Blood White

Grey Matter Light Gray

White Matter Medium Grey

CSF Near Black

Water Near Black

Air Black

CT image is determined only by degree to which tissues absorb X-ray

Bony str. Absorb large amount of x-rays and tend to obscure the details of neighboring structures poor visibility in brainstem.

Poor differentiation of grey-white pattern than compared to MRI.

Certain tumors may be invisible on CT because they absorb as much irradiation than the surrounding brain visible on Contrast CT.

Bone, clotted blood, calcified tissue, contrast material all appear white & CSF black

The only component of brain better seen on CT scan is Calcification, which may be invisible on MRI

Points to remember

Normal CT Brain

Criteria for Contrast- Patients with H/O seizurePatients with H/O cerebro-vascular accidentSuspicion of intracranial SOLs including granulomas,

CNS tumours, metastatic lesions

¤ Plain CT• Diagnostic accuracy 82%

¤ Contrast CT • IV iodinated contrast medium• Diagnostic accuracy 92%

Image showing enhancement after contrast administration

ADVANTAGES

Simpler, cheaper, more accessible

Tolerated by claustrophobics

No absolute contraindications

Better than MR for bone detail & Calcification

ADVANTAGES v/s DISADVANTAGES of CT

…Contd

DISADVANTAGES

Ionizing radiation

IV contrast complications

Limited range of tissue contrasts

Confusion &/or dementias of unknown cause First episode of psychosis First episode of major affective disorder after 50 years of age Personality changes after 50 years of age Psychiatric symptoms following head injury To rule out complications due to possible head trauma Prolonged catatonia Co existence of seizure with psychiatric symptoms Movement disorders of unknown etiology Focal neurological signs accompanying psychiatric symptoms

CLNICAL INDICATIONS OF CT BRAIN IN PSYCHIATRY

Weinberg 1984; Beresford et al 1986

MRI

Liquid Helium Cooled1.5 Tesla Solenoid Magnet

Patient Platform

RadiofrequencyTransmitter/Reciever

Coil

…ContdNuclei of all atoms are

thought to spin about an axis randomly oriented in

space

Placed in magnetic Field axis of all odd-numbered nuclei (mainly Hydrogen)

align with the magnetic field

When exposed to a pulse of radiofrequency waves - Axis

of nucleus deviates away from the magnetic field

When the pulse terminates, the axis of the spinning nucleus

realigns itself with the magnetic field

During this realignment, it emits its own

radiofrequency signal

MRI scanners collect the emissions of individual, realigning nuclei & use

computer analysis to generate a series of 2-D images that represent the brain

Radiofrequency and magnetic field pulses manipulated to create different pulse sequences.

Based on the duration of RF pulse & the length of time - different pulse sequences are obtained.

Examples: T1, T2, FLAIR, DWI etc.

T1 Weighted MRI

Best for visualizing normal neuroanatomy

Sharp boundaries between grey matter, white matter, and CSF

Useful in evaluation of cerebro-pontine angle cistern & pituitary fossa

Bone white white matter light grey grey matter medium grey water/CSF/air- Black

•T1 is the only sequence that allows contrast enhancement with Gadolinium.

•Contrast enhanced structures on T1 appears white.

T2 Weighted MRI

Less distinct boundaries between white and grey matter

Best for displaying pathology

Useful in demyelination, edema & tumour infiltration

Gray matter medium gray

white matter dark grey

CSF and water White

…Contd

T1 WEIGHTED IMAGES T2 WEIGHTED IMAGES

Fluid Attenuated Inversion Recovery (FLAIR)

Special type of MRI scan

T1 image is inverted & added to the T2 image

Contrast between grey & white matter is doubled & the normal CSF signal is suppressed.

Special indications1. To detect Sclerosis of

hippocampus in Temporal lobe epilepsy.

2. To Localize the areas of abnormal metabolism in degenerative neurological diseases.

Diffusion-Weighted Imaging (DWI)

Sensitive to speed of water diffusion

Visualizes area of ischemic stroke in 1st few hours- earliest to detect ischemia.

INDICATIONS

To rule out organic cause of psychiatric illness

Abrupt change in mental state

New onset memory loss or dementia

IMPORTANT POINTS•MRI magnets used in clinical practice ranges from 0.3 to 2.0 Tesla strength.•Higher field-strength scanners produce image of higher resolution.

ADVANTAGES

Does not expose the patient to ionizing radiations

Demyelinating disease can be assessed reliably

better study of posterior fossa structures

DISADVANTAGES

Avoided in patients wearing metallic devices

Claustrophobia

Does not pick up bony abnormalities

Difficult in uncooperative patients

CT Iodine based Iodine is highly attenuating of X-ray beam (bright on CT)

MRI Gadolinium based (Gadolinium DTPA) Gadolinium is a paramagnetic metal that hastens T1 relaxation of

nearby water protons (bright on T1-weighted images)

Tissue that gets brighter with IV contrast is said to be “enhanced”

Enhancement reflects the vascularity of tissue, The blood-brain barrier keeps IV contrast out of the brain Enhancement implies BBB is absent or dysfunctional

IV CONTRAST IN NEURO-IMAGING

Amygdala

Hippocampus

Caudate Head

Putamen

Globus Pallidus

Magnetic Resonance Spectroscopy

(MRS)

PRINCIPLE

Basic principle similar to MRI

Except

MRS can detect several odd-numbered nuclei

Permits study of many metabolic processes

φ Nuclei align themselves in the strong mag. field

φ A radiofrequency pulse causes the nuclei of interest to absorb & then emit energy

φ Readout on MRS in the form of a spectrum Can be converted into a pictorial image of the brain

NUCLEI USED IN MRS & Their uses in Psychiatry

NUCLEI USES

H¹ Decreased aspartate (NAA) in dementia & other neurological conditions

Li 7 Pharmacokinetics of Lithium

C¹³ Study of metabolic pathway

F 19 • Pharmacokinetics of certain drugs like SSRIs (Fluoxetine, Fluoxamine)

• Analysis of glucose metabolism

P³¹ Tissue metabolism (compound containing high energy phosphates like ATP, ADP etc.)

Significance of MRS in psychiatry

MRS has revealed decreased NAA conc. in temporal lobes & increased conc. of Inositol in occipital lobes of pts with Alzheimer dementia.

MRS has revealed decreased NAA conc. In temporal & frontal lobes of pts with Schizophrenia.

Also it has shown elevated brain Lactate levels during panic attacks in pts with panic disorder.

Functional Magnetic Resonance Imaging(fMRI)

A sub-type of MRI scan

Uses the New T2 or the Blood-Oxygen Level Dependent (BOLD) sequence Detects levels of oxygenated Hb in the blood Maps brain function

Detects not the brain activity per se, but the blood flow

Neuronal activity

within the brain

Local increase in blood

flow

Increases the local Hb conc.

Which reflects the

func. activity of brain on

T2 sequence

ADVANTAGES

• Possible to study both cerebral anatomy & functional neurophysiology using a single technique (Bullmore & Fletcher 2003)

• No radio active exposure

Limitations of fMRI

fMRI asseses neuronal activity indirectly by measuring blood flow (or tissue perfusion) this limits its resolution. Two tasks that activates clusters of neurons 5 mm apart

will yield overlapping signals on fMRI & thus are indistinguishable by this technique.

Sensitivity & resolution can be improved by using ultra-small non toxic iron oxide particles.

Acquisition of sufficient images for study can require 20 minutes to 3 hours, during which the subject’s head must remain in exactly the same position.

Depression group

fMRIHealthy Controls

Schizophrenia group

fMRIHealthy Controls

SPECT

SPECTSPECT

A type of Nuclear Imaging that shows how blood flows to tissues & organs Integrates : CT + Radioactive Material (Tracer) SPECT uses compounds labeled with single photon-emitting isotopes: iodine-

123, technetium-99m, and xenon-133

BASICS

…Contd

Inject with radio-labelled material

Gamma rays emitted detected

by scanner

Translated into 2-D image

These images added together

to get a 3-D image

Regional cerebral blood flow Tc 99 is most commonly used for deeper structures of brain Xe 133 for superficial structures of brain (rCBF Technique)

Muscarinic cholinergic system I 123

Dopaminergic system Radiolabelled receptor binding agents I123, IBZM (Iodobenzamide) for D2

receptors

Adrenergic system

Early diagnosis of Alzheimer's disease

USES

Regional brain function: perfusion

Dopamine D2 receptor availability

Dopamine transporter function

M1 muscarinic receptors

Nicotinic receptors

What SPECT can measure

Same scanner: different radio-pharmaceuticals

PET

BASIC PRINCIPLE

…Contd

g-ray detector +

-

Radioactive nucleus

• A radioactive isotope is injected & decays, emitting a β + particle.

• Within a short distance, the β + particle bumps into an electron & the two annihilate, producing a pair of g - rays.

• By detecting & reconstructing where the g - rays come from, we can measure the location & conc of radio-isotope.

Most Commonly Used Isotopes• F 18• N 13• O 15

To estimate regional cerebral blood flow

To estimate regional cerebral glucose metabolism (regional cerebral metabolic rate for glucose - rCMRglu)

For receptor imaging

To study normal brain development

APPLICATIONS

…Contd

SPECT v/s PET

SPECT PET

Single photon Positron

99mTc or I 123 11C or 18F

Short half life Longer half life

Less sensitive Highly sensitive (100 times more than SPECT)

Can buy isotopes Local cyclotron

Low spatial resolution Superior spatial resolution

Cheaper and easily available than PET

Costly, not easily available

Increased loss of gray matter in adolescence between the ages of 12-16 compared to healthy adolescence. Red—Gray Matter GainBlue—Gray Matter Loss

PET scan

PET ScanNot Depressed vs. Depressed

PET scans of a 45 year old woman with recurrent depression

pre and post treatment.

PET ScanADHD vs. Normal

White, Red, Orange = higher glucose metabolism

Blue, Green, Purple = lower glucose metabolism

NORMAL ADHD

IMAGING IN SPECIFIC PSYCHIATRIC DISORDERS

IMAGING IN DEMENTIA

ALZHEIMER’S DEMENTIA

Structural imaging

Cerebral atrophy (typical dilatation of lateral ventricles & widening of cortical sulci)-particularly in posterior temporal & parietal regions & specific brain regions like hippocampus and medial

temporal lobe.

Volumetric MRI reveals shrinkage in vulnerable brain regions, particularly the medial temporal lobe & Hippocampus.

Measurements of hippocampus is the most sensitive marker of pathology of AD early in disease

Functional imaging

Early studies using PET or SPECT revealed a characteristic pattern of hypometabolism in the posterior parietal lobes.

MRS in AD revealed- Decreased conc of NAA in the temporal lobes & increased conc of inositol in the occipital lobes

SPECT of rCBF in AD

(Cummings and Mega, 2003)

PET of Glucose Metabolism in normal vs. Alzheimer’s Disease

Recent..

Most recent development in brain imaging in AD is the development of radio-labelled ligands that can bind with amyloid, and then can be visualised with PET.This technique is currently under investigation.

FRONTO-TEMPORAL DEMENTIA

Structural imaging reveals- Severe sharply localised atrophy – bilaterally symmetric

“KNIFE-BLADE ATROPHY”

Hyper-intense signal in the cortex & underlying white matter of the affected areas

Areas involved- dorsolateral prefrontal cortex & medial temporal lobes

Areas spared- posterior parietal and occipital cortices.

Functional imaging reveals- Fronto-temporal hypometabolism

Frontal lobe dementia

Bi-lateral temporo-parietal deficits

Bi-lateral frontal lobe deficits

Alzheimer’s disease Frontal lobe dementia

• Frontal hypo-perfusion sometimes including temporal lobes

LEWY BODY DEMENTIA

To date, no MRI features have been identified to characterize DLB.

The absence of significant Medial Temporal lobe atrophy in an elderly demented patient suggests DLB etiology rather than AD.

PET or SPECT may reveal reduced occipital function with generalized reduction of cortical activity.

VASCULAR DEMENTIA

Vascular dementia

Multiple regions of focally reduced perfusion

NORMAL PRESSURE HYDROCEPHALUS

MRI findings include-

Ventricular enlargement out of proportion to sulcal atrophy.

Prominent periventricular hyperintensity (halo).

Prominent flow void in the aqueduct and third ventricle, the so-called jet sign, (presents as a dark aqueduct and third ventricle on a T2-weighted image where remainder of CSF is bright)

Thinning and elevation of corpus callosum on sagittal images

IMAGING IN OCD

-Frontal lobe -Caudate -Cingulate gyrus

Bilaterally smaller caudate in OCD pts.

Significantly more Cerebral Grey matter & Less white matter volume than normal controls.

Decreased volume of Left orbital frontal cortex.

Abnormality in length of Corpus callosum.

Abnormality in Pituitary volume may also be noted.

Larger anterior cingulate volumes (ACV) a/w increased OCD symptoms severity but not duration of illness

CT & MRI IN OCD

OCD patients were divided into three groups Responders to a SSRI Responders to a SSRI + an Atypical

Antipsychotic Non-Responders to either SSRI or

SSRI + an Atypical Antipsychotic

MRS was used to measure NAA concentrations in the anterior cingulate, the left basal ganglia & the left prefrontal lobe of the subjects

Significantly lower NAA concentrations in responders to SSRI + AAP in anterior cingulate gyrus

MRS IN OCD

Sumitani S et al (2007) Psychiatry Res; 154: 85-92

Greater Glutamatergic conc. in caudate, as measured by ¹H-MRS in comparison to controls

SPECT & PET in OCD

In a resting SPECT study, OCD pts has increased mesial frontal perfusion, which normalised with fluoxetine Rx.

PET have shown- Increased activity (eg. Metabolism & blood flow) in the frontal lobes, basal ganglia(sp. caudate), and the cingulate gyrus in OCD pts. (findings consistent with the MRI findings)

Head of the caudate PET : Greater activity SPECT : Decreased activity

Pharmalcological and behavioral Rx reportedly reverse these abnormalities.

IMAGING IN DEPRESSION& BIPOLAR DISORDER

-Left Prefrontal cortex-Subcortical nuclei

CT & MRI in Depression

Smaller volumes of frontal cortex, cerebellum, caudate & putamen.

Ventricular enlargement, cortical atrophy, and sulcal widening also have been reported in some studies.

The most consistent abnormality observed in depression is- Increased frequency of abnormal hyperintensities in subcortical regions including periventricular regions, basal ganglia, and thalamus. These hyperintensities may reflect the deleterious effects of recurrent

affective episodes. (specially in bipolar I disorder and among elderly)

Some depressed pts may also have specifically reduced hippocampal or caudate nucleus volumes, suggesting presence of more focal defects. Focal areas of atrophy have been associated with increased

illness severity, bipolarity and increased cortisol levels.

Bilateral anterior cingulate cortex & Right amygdala significantly smaller in size.

Inactivation of Left prefrontal cortex in Depressed

fMRI IN DEPRESSION

Tang Y et al (2007) Psychiatry Res.

Inactivation of Right prefrontal cortex in Mania

Depression group

fMRIHealthy Controls

Baseline cerebral blood flow (CBF) was lower in depressed patients – in frontal cortex & subcortical nuclei bilaterally

Medication response – normalization of CBF deficit.

SPECT in Depression

Joensuu M et al (2007) Psychiatry Res. 154(2): 125-31

PET in Depression

The most widely replicated PET finding in depression is- Decreased anterior brain (frontal / prefrontal cortex) metabolism specially on dominant hemisphere (LEFT side). Reversal of this hypofrontality occurs when

pt. shifts from depression into mania (i.e. decrease RIGHT frontal lobe function seen in mania)

It has been seen that antidepressants at least partially NORMALISES these changes.

PET scans of a 45 year old woman with recurrent depression

pre and post treatment.

Bipolar disorder PET studies in depressed BPI, bipolar II, and manic

individuals have shown increased amygdala and ventral striatal limbic subcortical activity compared with healthy controls

In adults, there are findings of enlarged (or shrunken) amygdalae, decreased dorsal and ventral prefrontal cortices, and smaller or no change in hippocampi.

Altshuler LL, Bartzokis G, Grieder T, et al. An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia. Biol Psychiatry. 2000;48:147–162.

Blumberg et al. 2003 "Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder". Arch Gen Psychiatry 60 (12): 1201–8.

IMAGING IN SCHIZOPHRENIA

Structural imaging Enlargement of lateral & third ventricles may be static or

progressive.

Frontal lobe abnormalities, particularly prefrontal gray matter and orbitofrontal regions.

Parietal lobe abnormalities, particularly of the inferior parietal lobule which includes both supramarginal and angular gyri.

Subcortical abnormalities i.e. cavum septi pellucidum, basal ganglia, corpus callosum, and thalamus.

All these structural abnormalities may be static or progressive.

Decreased size of medial temporal lobe structures (which include the amygdala, hippocampus, and parahippocampal gyrus), and abnormalities of neocortical temporal lobe regions (superior temporal gyrus).

Hippocampus is not only smaller in size but also functionally abnormal (disturbed glutamate transmission in functional scans)

Reduced symmetry in various brain areas may be indicative of disruption of brain lateralisation during neurodevelopment.

Anatomical & functional deficits in prefrontal cortex.

Volume shrinkage or neuronal loss in medial dorsal nucleus of thalamus.

Positive symptoms Decreased volume of Superior temporal gyrus

Negative symptoms Enlarged lateral ventricle & decreased volume of medial temporal lobe structures

Typical Anti-psychotics increases the size of the basal ganglia

Ventriculomegaly in discordant monozygotic twins seen on T2-weighted MRI scans.

Woolley J , and McGuire P APT 2005;11:195-202

©2005 by The Royal College of Psychiatrists

Functional imaging Hypofrontality

Functional scans have also revealed lower levels of phosphomonoester & inorganic phosphate and higher levels of phophodiester in schiz pts.

NAA levels were also lower in hippocampus and frontal lobes in pts with schiz.

Scan showing Increased loss of gray matter in adolescence between the ages of 12-16 compared to healthy adolescence. Red—Gray Matter Gain ; Blue—Gray Matter Loss

IMAGING IN ANXIETY D/Os

Structural imaging (CT & MRI)-Occasional increase in size of ventricles.Abnormalities in RIGHT hemisphere but not in the left

hemisphere.○ This finding suggests that some type of cerebral

asymmetry may be important in the development of anxiety disorder.

Functional imaging (fMRI, SPECT, PET)-Abnormalities in frontal cortex, occipital & temporal

areas in pts. with anxiety disorder & Abnormalities in parahippocampal gyrus in pts with panic disorder.

MRS – In panic d/o used to record the levels of lactate,

whose IV infusion can ppt. panic episodes in ~ 3/4th of the pts. with either Panic D/o or Major Depression

Brain lactate conc. were found to be elevated during panic attacks, even without provocative infusion in panic disorder pts.

IMAGING IN PTSD

Structural imaging in PTSD

Studies in PTSD Vietnam combat veterans revealed:Reduced left and right hippocampal

volumeVolume reductions were associated

with severity of combat exposure. A similar study was undertaken with Gulf

war veterans in Israel, and these data are have shown similar findings

Boone, Omar et al. Longitudinal MRI Study of Hippocampal Volumein Trauma Survivors With PTSD. Am J Psychiatry 2001; 158:1248–1251

Hippocampus (green), Fornix (blue) and Mammilary Bodies (gray) are shown in 3D.

Smaller hippocampal volume is not a necessary risk factor for developing PTSD and does not occur within 6 months of expressing the disorder

This brain abnormality might occur in individuals with chronic or complicated PTSD.

Boone, Omar et al. Longitudinal MRI Study of Hippocampal Volumein Trauma Survivors With PTSD. Am J Psychiatry 2001; 158:1248–1251

Twin studies in PTSD A study reported in Nature-Neuroscience evaluated MR

brain morphometry of the hippocampus in monozygotic twins discordant for PTSD. The PTSD twin was diagnosed with PTSD as a result of combat exposure in the Vietnam War.

The twin aspect of this study was important as it showed that individuals discordant for PTSD showed reduced hippocampal volume compared with twins where PTSD was present in neither twin.

This finding suggests that there may be a predisposition or vulnerability factor involved in the genesis of PTSD

Gilberson, MW et al. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nature-Neuroscience, October 2002

Functional imaging in PTSD

fMRI studies have found increased activity in Amygdala, a brain region associated with fear.

IMAGING IN ADHD

Structural imaging (CT & MRI)

Shows no consistent findings.

Increased cortical grey & white matter volumes from 5 yrs of age with peak at 12-15 yrs of age.

Early onset ADHD may be associated with smaller total brain volume in- 4% cases.

Decrease in the volume of posterior inferior cerebellar vermis may be noted.(region involved in attention processing)

Functional imaging (fMRI, SPECT, PET)

PET has shown that adolescent females with ADHD have globally lower glucose metabolism that both normal controls & males with ADHD.

PET scan has also shown lower CBF and metabolic rates in the frontal lobes of children with ADHD.

This may be because frontal lobes in children with ADHD are not adequately performing their inhibitory mechanism on lower structures, leading to disinhibition.

Less striatal activation during cognition inhibition tasks.

PET ScanADHD vs. Normal

White, Red, Orange = higher glucose metabolism

Blue, Green, Purple = lower glucose metabolism

IMAGING IN AUTISM

Structural imaging Significant DECREASE of grey matter concentration in superior

temporal sulcus bilaterally, an area which is critical for perception of key social stimuli.

Also a decrease of white matter concentration in the right temporal pole and in cerebellum compared to normal children.

INCREASE in total cerebral volume, both in grey and white matter, mostly in the occipital, temporal and parietal lobes.

Brain enlargement has been considered as a possible biomarker for autistic disorder.

Functional imaging

Bilateral hypoperfusion of the temporal lobes in autistic children.

In addition, activation abnormalities may be observed in the temporal lobes and amygdala, which are involved in language and social cognition.

An increase in visual cortex activity was also reported

Message… Neuroimaging can be structural / functional

Functional imaging more useful than structural in psychiatry

Neuroimaging in psychiatry is presently used mainly to rule out neurological causes, and in evalulation of dementia

Sensitiviy & specifity of imaging in psychiatry is not much

Still various studies and their findings and newer developments holds a promising future for neuroimaging in psychiatric diagnosis & managements.

Presented and Made by-

Dr.Swapnil AgrawalResident- Psychiatry

Govt. Medical College, Kota (Raj)

dr.swapnil@yahoo.co.in